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      • The role of B cells and alloantibody in chronic cardiac allograft rejection

        Wehner, Jennifer Rose The Johns Hopkins University 2010 해외박사(DDOD)

        RANK : 247343

        Increasingly effective methods of preventing and treating rejection in cardiac transplant recipients have increased patient survival, but graft loss due to chronic rejection remains a barrier to long-term graft survival. Immunosuppressive regimens that currently focus on targeting T cells have decreased the amount of graft loss due to acute cellular rejection, however, rejection due to antibody mediated processes remains. Although the presence of B cells and plasma cells has been characterized in kidney transplants, their presence had not previously been described in human cardiac transplants. We have characterized the prevalence and patterns of distribution of B cells and plasma cells in human cardiac transplants with chronic rejection. In our study, we evaluated 16 cardiac allografts removed at retransplant because of chronic rejection. We found that B cells and plasma cells were a consistent finding in and around coronary arteries with chronic rejection. Many of the infiltrates formed nodules, some of which had distinct compartmentalization similar to tertiary lymphoid nodules. The frequency of B cells and plasma cells within and surrounding vessels with allograft vasculopathy was significantly higher than in coronaries with native atherosclerosis or surgical procedures. We extended our findings in humans to develop a mouse model where the role and interactions of B cells, T cells, and alloantibodies could be tested. We have developed a SCID mouse model where minimal numbers of T cells can be transferred with larger populations of B cells or monoclonal alloantibodies. The transfer of CD4 T cells resulted in the maximal T cell and macrophage infiltration into the graft and the greatest degree of vascular pathology. Surprisingly, the transfer of B cells or alloantibody with naive CD4 T cells dampened the infiltration and vascular damage to the graft. Our work suggests that B cells and alloantibody interact with T cells to modulate immune responses to cardiac allografts.

      • "A lot up for grabs": The conversion narrative in modernity in Kate Chopin, Flannery O'Connor, and Toni Morrison

        Wehner, David Zahm University of Minnesota 2005 해외박사(DDOD)

        RANK : 247343

        For two thousand years, Western literature has given us conversion narratives, stories recounting the moment the protagonist "turns round," the translation of the Latin convertere from which we get conversion. In the West, these stories have a long history in and association with Christianity, so this dissertation begins with a simple question: what happens to the conversion narrative in modernity, where Christianity no longer has a "taken-for-granted" status, to use Peter Berger's phrase, and becomes "one system among others," to use Niklas Luhman's? To answer this question, this study closely examines the works of Kate Chopin, Flannery O'Connor, and Toni Morrison, writers chosen because they each produce modern conversion narratives---some religious, some secular---and because they provocatively engage with the larger project behind this study, mapping the landscape of religion and secularism in modernity. In part, this landscape looks like the work of Kate Chopin, a woman raised Catholic, who leaves the specifics of doctrine as an adult and combines her religious temperament with readings in Ralph Waldo Emerson and Charles Darwin to form an idiosyncratic, syncretic religion of one, ignoring binaries of religion and science, spirit and matter. It looks like the work of Flannery O'Connor, a writer whose Christian faith never wanes and who instead spends her writing career critiquing the secularism of her culture, embodied, for her, in such figures as Emerson, Sigmund Freud, and Carl Jung. And, finally, it looks like the work of Toni Morrison, an author who combines her sense of writing from "a nonsecular space" with her sense of being a black woman in a racist, patriarchal culture. The conversion of many of her characters, then, is a conversion of racial consciousness, a transformation that for the author carries religious import. Modernity has not led to secularism, as once thought it would, but has led to a pluralism of systems rubbing against and vying with one another. This study theorizes a literary genre and uses that genre to approach these three writers in a different manner in order to open out to the larger project of delineating this pluralism.

      • Crafting lives, crafting society in seventeenth-century Jamestown, Virginia

        Wehner, Karen Bellinger New York University 2006 해외박사(DDOD)

        RANK : 247343

        In planting the first permanent New World English settlement at Jamestown in 1607, the Virginia Company hoped to replicate profits made through diversified investment in town-based industries in England and overseas. While colonial commerce took off with tobacco, commodity extraction and manufacturing efforts at Jamestown sputtered, despite vigorous recruitment and generous incentives for skilled emigrants. The failure of Jamestown's economy to diversify as planned has been attributed to tobacco's success, and tobacco has been blamed for the failure of "real" towns---much less industry---to flourish in the seventeenth-century Chesapeake. This dissertation contends that the propaganda-laden documentation of industrial-scale failures such as the Glasshouse and Falling Creek ironworks overshadow evidence for the viability of smaller-scale craft production in Jamestown. If acknowledged previously, such craft efforts have been sentimentalized as the root of a "great industrial nation," or dismissed as failed experiments, doomed by tobacco in post-Company Virginia. This dissertation presents historical and archaeological evidence that artisans labored at Jamestown throughout the seventeenth century, both independently and sponsored by entrepreneurial elites. Evidence for higher relative upward mobility among artisans suggests that the interface between artisanship and the dominant agricultural economy was complex rather than simple. Replicating English labor and capital investment strategies, Jamestown's craft practitioners and sponsors pursued diversified paths to crafting new lives in Virginia. Land records, court documents and artifact distributions combine to produce case studies linking material evidence for crafting with known artisans and entrepreneurs at Jamestown. This activity is situated within the broader context of English Atlantic colonizing efforts. The dissertation builds on a century of excavations at Jamestown by using Geographical Information Systems (GIS) technology to re-provenience; the massive Jamestown archaeological collection curated by the National Park Service. For the first time, spatial analysis in the townsite includes plowzone deposits which---despite comprising over 75% of the collection---have been excluded from previous synthetic analyses. My findings call for complication of what has been assumed concerning opportunities for free artisans in the early Chesapeake, and of everyday Jamestown life more generally.

      • Protein-RNA interactions: The key to ribosome biogenesis and pre-rRNA processing

        Wehner, Karen Alexandra Yale University 2002 해외박사(DDOD)

        RANK : 247343

        Ribosomes are responsible for production of proteins required for cellular maintenance, growth and survival. Many of the steps in ribosome biogenesis have been elucidated by studies in <italic>S. cerevisiae</italic>, but most of the ribonucleoprotein and protein factors required for these steps are conserved throughout evolution. The small subunit rRNA and two of the large subunit rRNAs are transcribed as a large polycistronic transcript. As a result a complex series of processing steps are required to separate the large and small subunit rRNAs. The U3 processome is required for production of the small ribosomal subunit RNA, the 18S rRNA. Specifically, the U3 processome is essential for formation of a conserved structure within the 18S rRNA and for cleavages of the pre-rRNA, both of which are required for 18S maturation. To further elucidate how U3 mediates these events, the regulatory and mechanistic roles of the U3 specific proteins: Imp3p, Imp4p and Mpp 10p were examined. The three proteins were found to form an interdependent unit that is crucial to U3 function. Based on similarity to the Imp4 protein, a novel superfamily of RNA binding proteins whose members are required for different stages of ribosome biogenesis was identified. The Imp4 superfamily is composed of five individual families (Imp4, Rpf1, Rpf2, Brx1 and Ssf) that all possess the σ<super>70</super>-like motif, a novel eukaryotic RNA binding domain with prokaryotic origins. The Imp4 superfamily members associate with RNAs that are consistent with their distinct roles in ribosome biogenesis.

      • Living in style: Marketing, media, and the discovery of lifestyles

        Wehner, Patrick T Emory University 2000 해외박사(DDOD)

        RANK : 247343

        An interdisciplinary American Studies project combining media studies, business history, and the sociology of culture, “Living in Style” traces the emergence of “lifestyles” as a way for marketing and media decisionmakers to imagine social life in the United States. Using materials like trade journals, business texts, and personal memoirs, the dissertation explores how the notion of “lifestyles” has been defined within the professional spheres of business and journalism since the end of the Second World War. The first chapter, “Containing Multitudes,” examines the classifications employed by early twentieth century newspaper managers to better understand their society. The chapter considers the relationship between evolving concepts of the audience and the appearance of special categories of content, including the newspaper “women's pages.&rdquo. Chapter Two, “The Rise of an Entrepreneurial ‘Class’” documents how “lifestyles” were introduced to marketing. Responding to an “society of abundance” that made earlier models of consumption suspect, the first generation of professional consumer researchers promoted class and “life-styles” as classifications for dividing the marketplace and making its workings understandable. But many of these researchers also regarded themselves as championing creativity and warding off suburban conformity. Chapter Three, “Across the Great Divide,” describes how lifestyles became a standard feature of the news. In particular, the chapter examines the decision by editors to replace their women's sections with “lifestyle” coverage beginning in the late 1960s. In what was perceived as an era of change, “lifestyle” sections helped address fears that newspapers were out of touch with the daily lives of readers. By the 1970s, however, these sections were being employed to promote an upscale, cosmopolitan audience. The final chapter, “Living in Style” suggests a shared model of identity has further blurred the boundaries between marketing and the media. As lifestyle databases have developed into a multi-million dollar industry, these same classifications have emerged as a standard means of evaluating media audiences. Like the dissertation as a whole, this chapter proposes that despite, or even because of its ambiguity, the notion of “lifestyles” remains at the center of a pervasive and inherently political way of seeing our world today.

      • Lower extremity exoskeleton as lift assist device

        Wehner, Michael University of California, Berkeley 2009 해외박사(DDOD)

        RANK : 247343

        United States workplace injury data demonstrates that in 2005 overexertion caused more than 270 000 cases of lower back disorders (LBD) severe enough to cause absenteeism. This amounts to more than one case reported for every ten warehouse manual material handlers in one year. Manual material handling remains a physically demanding task and existing assist devices have found limited success. Extensive research has been performed on workplace back loading, and several biomechanical models have been developed to study the issue. We propose a lower extremity exoskeleton device which adds a passive extensor moment (restoring moment) about the hips and acting on the upper torso when a wearer is in non-neutral bending and squatting postures, thus reducing forces on the lower back by (1) decreasing the required extensor muscle force, and (2) transmitting forces directly to the ground via the exoskeleton structure. The maximum useful moment profile (providing the greatest restoring moment, yet comfortable for the wearer) was determined via iterative adjustments and oral interviews with six subjects. Video sequences were recorded of normal speed sagittal squat lifting a 44.5 N (10 lb) and a 133.5 N (30 lb) package with retro-flective markers. Marker locations were tracked, and forces were computed for static and dynamic cases. Surface electromyography (EMG) was performed on 6 subjects to measure muscle activation in the static squat posture: supporting 44.5 N (10 lb) and 133.5 N (30 lb) packages. Biomechanical model calculations based on marker tracking data suggested that the device significantly reduces maximum erector spinae muscle tension and spine compressive forces when lifting 133.5 N (30 lb) and 44.5 N (10 lb) packages. Static EMG analysis with 133.5 N (30 lb) and 44.5 N (10 lb) packages showed that with the moment restoring exoskeleton, subjects also demonstrated a significant reduction in muscle activity, confirming results found using the biomechanical model. Dynamic EMG testing with 133.5 N (30 lb) and 44.5 N (10 lb) packages showed statistically significant reduction in average back muscle activation over the course of the lift. The lower extremity exoskeleton effectively reduces low back forces during squat lifting. These results correlate to similar studies of the low back and of other lift assist devices. This exoskeleton device includes features not available on other devices including real-time adjustability of moment profile, ability to reduce moments in squat position, and eliminating high contact stress in the lower extremities by connecting directly with the ground.

      • From graduate to seasoned practitioner: A qualitative investigation of genetic counselor professional development

        Zahm, Kimberly Wehner University of Minnesota 2009 해외박사(DDOD)

        RANK : 247341

        Research on professional development processes can contribute to individuals' anticipation and normalization of developmental processes, to improved training and supervision, and to the creation of a wider breadth and depth of professional development opportunities and support in the field. Presently, no comprehensive studies of genetic counselor professional development have been conducted. In the present study 34 post-degree genetic counselors from all six National Society of Genetic Counselors practice regions in the United States and Canada participated in a semi-structured telephone interview about their professional development experiences. Five major research questions were investigated: (1) What constitutes professional development for genetic counselors? (2) How do these professional development processes occur for genetic counselors? (3) What facilitates and/or impedes professional development? (4) How does genetic counselor professional development vary as a function of experience level? and (5) How does genetic counselor professional development compare/contrast to psychotherapist development described by Skovholt and Ronnestad (1992a)/Ronnestad and Skovholt (2003) and Orlinsky et al. (2005)? Participants were purposefully sampled from three levels of post-degree genetic counseling experience: novice (0-5 years), experienced (6-14 years), and seasoned (≥ 15 years). Using a modified version of Consensual Qualitative Research (Hill et al., 2005; 1997), three themes, 12 domains, and 47 categories were extracted from data. The themes are: (1) Being a clinician: Genetic counselors' evolving perceptions of and relationships to their clinical work; (2) The field itself: Genetic counselors' evolving perceptions of and relationships to the field of genetic counseling; and (3) Being a clinician in the field: Genetic counselors' evolving perceptions of and relationships to their role as a genetic counselor. A preliminary model of genetic counselor professional development is proposed. The model suggests development processes occur throughout the professional lifespan, each component of professional development mutually influences the others, and there are both positive and negative avenues of development. For instance, personal life and professional life mutually influence each in important ways. Participants rated 15 influences on their professional development (adapted from Orlinsky et al., 2005). Within and across experience levels, and consistent with Orlinsky et al.'s (2005) findings, sources of interpersonal influence ("experiences in genetic counseling with patients" and "working with genetic counseling colleagues") were rated as highly important. The findings also were largely consistent with Skovholt & Ronnestad's (1992a/2003) therapist model (anxiety in early practice dissipating over time, personal life affecting professional development, etc.), with a few notable differences (including unique challenges of frequently delivering "bad news" to patients, and the parallel process between individual counselors' professional development experiences and genetic counseling's development as a relatively young field. Major findings, study strengths and limitations, and practice, training, and research implications are discussed.

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